DJ-1 promotes angiogenesis and osteogenesisby activating FGF receptor-1 signaling

摘要

Communication between osteoblasts and endothelial cells is essential for bone fracturerepair, but the molecular identities of such communicating factors are not well defined. Herewe identify DJ-1 as a novel mediator of the cross-talk between osteoblasts and endothelialcells through an unbiased screening of molecules secreted from human mesenchymal stemcells during osteogenesis. We show that DJ-1 stimulates the differentiation of humanmesenchymal stem cells to osteoblasts and that DJ-1 induces angiogenesis in endothelialcells through activation of fibroblast growth factor receptor-1 signalling. In a rodent model ofbone fracture repair, extracellular application of DJ-1 enhances bone regeneration in vivo bystimulating the formation of blood vessels and new bones. Both these effects are blocked byantagonizing fibroblast growth factor receptor-1 signalling. These findings uncover previouslyundefined extracellular roles of DJ-1 to promote angiogenesis and osteogenesis, suggestingDJ-1 may have therapeutic potential to stimulate bone regeneration.